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PHLDA2 (Pleckstrin homology-like domain, family A, member 2)

Written2020-10Renan Gomes do Nascimento, Flavia Rotea Mangone Ana Carolina Pavanelli, Maria Aparecida Nagai
Disciplina de Oncologia, Departamento de Radiologia e Oncologia, Faculdade de Medicina, Universidade de São Paulo, 01246-903, São Paulo, Brasil (RGN, NMA), Laboratório de Genética Molecular, Centro de Investiga&ccdil;ão Translacional em Oncologia, Instituto do Câncer do Estado de São Paulo (ICESP), 01246-000, São Paulo, Brasil; (RGN, FRM, ACP, NMA)

Abstract Review of the PHLDA2 gene, with data on DNA, the protein encoded by this gene, and biological and pathological implications.

Keywords PHLDA2; genomic imprinting; glycogen storage; apoptosis; cell-cycle; epithelial-mesenchymal transition

(Note : for Links provided by Atlas : click)


HGNC Alias symbIPL
HGNC Previous nameTSSC3
HGNC Previous name"tumor suppressing subtransferable candidate 3
 pleckstrin homology-like domain, family A, member 2"
LocusID (NCBI) 7262
Atlas_Id 41708
Location 11p15.4  [Link to chromosome band 11p15]
Location_base_pair Starts at 2928273 and ends at 2929420 bp from pter ( according to GRCh38/hg38-Dec_2013)  [Mapping PHLDA2.png]
Fusion genes
(updated 2017)
Data from Atlas, Mitelman, Cosmic Fusion, Fusion Cancer, TCGA fusion databases with official HUGO symbols (see references in chromosomal bands)
Note PHLDA2 gene was mapped on human chromosome 11p15.5, considered an important region comprising human tumor suppressor genes (Qian et al., 1997; Hu et al., 1997). This gene exhibits a monoallelic expression by genomic imprinting with preferential expression of the maternal allele (Lee & Feinberg, 1998). Phylogenetic analyses classify PHLDA2 as a member of the pleckstrin homology superfamily (PHL), including PHLDA1 and PHLDA3 (Frank et al., 1999; Saxena et al., 2002). The PHLDA2 gene consists of 1,148 base pairs, 2 exons, and 1 intron, encodes a 9.2 kb mRNA with a coding region of 458 bp. 


Description DNA size: 1,148 kb, 2 exons.
Transcription mRNA size 920 pb NM_003311.4. Only one transcript variant encoding PHLDA2 have been described. NM_003311 - Homo sapiens pleckstrin homology-like domain, family A, member 2 (PHLDA2), mRNA -> Transcript size: 920 bp. NP_003302.1. (;


  Figure 1. Schematic representation of the modular structure of the PHLDA2 protein. The PHLDA2 protein structure consists of a single PHL domain (pleckstrin homology-like) from amino acid residues 7 to 99, flanked by short terminal extensions.
Description The protein encoded by the PHLDA2 gene consists of 152 amino acids, a molecular weight of 17.1 kDa, composed mainly of the PHL domain (93aa) (Frank et al., 1999). The PHL domain present in its structure has a moderate binding affinity to phosphatidylinositol 4,5-bisphosphate (PIP2) and phosphatidylinositol 3,4,5-triphosphate (PIP3) (Frank et al., 2002; Saxena et al., 2002). NP_003302.1 (
Expression According to the integrative human mRNA and protein expression map, the PHLDA2 is remarkably expressed in placental tissue. Tissues of stomach, colon, prostate, duodenum, small intestine, and kidney are those of more abundant expression (Fagerberg et al., 2013). A monoallelic expression is observed in human fetal tissues such as the kidney, intestine, liver, heart, being the maternal allele preferentially expressed (Lee & Feinberg, 1998). It has been shown that PHLDA2 expression is down-regulated under hypoxia in human trophoblasts (Roh et al., 2005). PHLDA2 has been described as the first apoptotic related gene regulated by genomic imprinting (Lee & Feinberg, 1998). PHLDA2 expression is negatively regulated at the minimum by two different mechanisms, one by at least to miRNAs ( MIR214 MIR148A-5p) and by a methyltransferase called EZH2 (Lv et al., 2015; Idishi et al., 2018; Li et al., 2019).
Localisation The mature PHLDA2 protein subcellular localization is at the cytoplasm, cellular membrane, and also peripheral membrane protein (
Function The PHLDA2 gene is one of several genes clustered at 11p15.5 domain, an important region for tumor suppressor genes. Changes in this chromosomal region have already been described in Beckwith-Wiedemann syndrome, hydatidiform mole, and different types of tumors (Hu et al., 1997, Weksberg et al., 2005, Feinberg, 1999).
The protein encoded by the PHLDA2 gene can play different biological roles depending on cell or tissue specificity ( In mouse models, PHLDA2 negatively controls glycogen storage during pregnancy, negatively regulates the expression of a variety of placental hormones through the spongiotrophoblast layer (Tunster et al., 2010; Tunster et al., 2016).
PHLDA2 (TSSC3) has been shown to induce apoptosis by increasing the intrinsic pro-apoptotic pathway members such as BAK1, BCL2L11 (BIM), CYCS (Cyt c), and the BAX: BCL2 ratio and downregulating anti-apoptotic proteins like BCL2 and FAS in human osteosarcoma cell lines (Dai et al., 2012; Huang et al., 2012). PHLDA2 has also been shown to have a role in anoikis resistance and metastasis through the interaction with RANBP9 and downregulation of the SRC -dependent Akt pathway in osteosarcoma cells (Dai et al., 2016).
Experimental evidence also associated increased expression of PHLDA2 in trophoblast cells with cell-cycle inhibition through the reduction of cyclin D1 and cyclin E ( CCND1 and CCNE1) arresting cells in G0/G1 phase of the cell cycle (Jin et al., 2015).
PHLDA2 increases epithelial-mesenchymal transition (EMT) of osteosarcoma cells by upregulating mesenchymal markers, such as CDH2 (N-cadherin), VIM (Vimentin), and SNAI1 (SNAIL), and inhibiting the epithelial markers like CDH1 (E-cadherin) (Dai et al., 2016, Lv et al., 2016). Additionally, PHLDA2 can inhibit Src/Akt pathway suppressing self-renewal in osteosarcoma stem cells (Yan et al., 2017), and this Src/Akt pathway inactivation prevents MTOR phosphorylation, that drives osteosarcoma cells to autophagy, contributing to the inhibition of tumorigenesis and metastasis (Zhao et al., 2018).
  Figure 2 - Schematic diagram of the modulators, effectors, and biological processes associated with PHLDA2 expression. Different stimuli can modulate PHLDA2 expression. Therefore, various biological processes are associated depending on the stimulus and cellular effectors.
Homology The human protein encoded by the PHLDA2 gene is highly conserved in vertebrates. Orthologs have been described in Pan troglodytes (chimpanzee); Macaca mulatta (Rhesus monkey); Bos taurus (cattle); Mus musculus (house mouse); Rattus norvegicus (Norway rat); Gallus gallus (chicken), Xenopus tropicalis (tropical clawed frog), Danio rerio (zebrafish) (, among others also described at Ensembl genome browser ( PHLDA2 ENSG00000181649, Ensembl release 100 - April 2020). Moreover, two protein paralogues are known: PHLDA1 (pleckstrin homology like domain, family A, member 1) e PHLDA3 (pleckstrin homology like domain, family A, member 3) ( PHLDA2 ENSG00000181649)

Implicated in

Note The PHLDA2 gene is located in a chromosomal region considered an important center for imprinting and localizing tumor suppressor genes. Alterations in the expression of PHLDA2 has been reported in different types of tumors. However, the attribution of its oncogenic or suppressive functions in tumor development is under investigation (Dai et al., 2012; Hsu et al., 2017; Zhao et al., 2018).
Entity Placental and Fetal Development
Note Several reports in the literature have been shown the role played by PHLDA2 expression in placental development. Salas et al. (2004), using a transgenic model, demonstrated that loss of Phlda2 expression in animals with wild background causes placentomegaly and increased expression of this gene in the placenta causes a significant delay in placental growth. High expression of the PHLDA2 leads to decreased expression of genes associated with lipids production, regulated by spongiophoblasts, causing placental dwarfism and reduction in the accumulation of placental glycogen (Tunster et al., 2016). High expression of PHLDA2 was also significantly associated with decreased birth weight, showing that PHLDA2 can act to decrease body weight by reducing the size and function of the placenta (Apostolidou et al., 2007). The expression of PHLDA2 in the placenta was significantly correlated with decreased femur growth in fetuses between 19 and 34 weeks of gestation and later associated with a lower bone mineral content of the child at the age of four (Lewis et al., 2012).
PHLDA2 expression has been associated with hydatidiform mole disease, in which an increase in PHLDA2 expression was observed in trophoblast cells, possibly due to trisomy of the 11p15.5 chromosomal region (Fisher et al., 2004).
PHLDA2 expression has also been associated with the development of spontaneous abortions, where the increased expression of this gene was observed in placental and fetal samples in the first half of the interrupted pregnancy, showing that this gene may be a possible marker in fetal growth. In vitro studies, with trophoblast cells with overexpression of PHLDA2, showed inhibition of cell growth, migration, and invasion. On the other hand, PHLDA2 reduced expression showed the opposite effect, with an increase in migration and invasion, suggesting the involvement of PHLDA2 in the development of pre-eclampsia due to inhibition of proliferation, migration, and invasion of trophoblastic cells (Jin et al., 2015).
Entity Lung cancer
Note High expression of PHLDA2 was observed in samples of lung adenocarcinoma compared to adjacent normal tissue. Increased PHLDA2 expression was associated with poor patient survival, suggesting an oncogenic role of PHLDA2 in the development of lung cancer (Hsu e al., 2017). PHLDA2 was also identified as negatively regulated in lung cancer cell lines after inhibiting the EGFR/ ERBB2 pathway. In addition, PHLDA2 expression showed a direct correlation with the expression of p-AKT, suggesting that PHLDA2 may act in the regulation of oncogenic signaling pathways (Wang et al., 2018).
Entity Osteosarcoma
Note In osteosarcomas, PHLDA2 has been investigated and reported as a possible gene with tumor-suppressive activities. Osteosarcoma samples showed reduced expression of PHLDA2 when compared to adjacent normal tissue and were found to be associated with clinical-pathological data, such as high tumor grade, presence of metastasis, and tumor recurrence (Dai et al., 2012; Wang et al., 2016). PHLDA2 knockdown results in increased cell proliferation and colony formation decreased cell division and apoptosis, and increased tumor growth, which suggests that inactivation of the PHLDA2 protein may contribute to the development and progression of these tumors (Dai et al., 2012). Osteosarcoma cells with PHLDA2 overexpression show increased autophagy and reduced MTOR phosphorylation via SRC/AKT, leading to suppression of tumorigenesis and metastatic phenotype (Zhao et al., 2018). Recently, negative regulation of PHLDA2 expression has been associated with MIR214 expression, promoting resistance to radiotherapy, pulmonary metastasis, and activation of the AKT pathway, suggesting that PHLDA2/AKT may be a new radiotherapy target in osteosarcomas (Yi Li, et al. 2019).
Entity Pancreatic adenocarcinoma
Note Pancreatic adenocarcinoma is one of the most lethal cancers, in which only 5% of patients have recurrence-free survival in 5 years. Low expression of PHLDA2, directly modulated by MIR148A-5p, inhibits proliferation, migration, and invasion and increases apoptosis in PANC-1 cells, which are derived from pancreatic carcinoma (Idich et al., 2018).
Entity Colorectal cancer
Note A recent study found that colorectal tumors showed higher expression of PHLDA2 (transcripts and proteins) when compared to adjacent normal tissues. The inactivation of these proteins in colorectal cancer-derived lineage promoted inhibition of cell growth, migration and invasion, and reduced expression of proteins related to the epithelium-mesenchymal transition, and induction of autophagy through the PI3K/AKT signaling pathway, suggesting that PHLDA2 may play a role in the development and progression of colorectal cancer (Zhan Ma et al., 2020).
Entity Breast cancer
Note There are few studies in the literature addressing the expression of PHLDA2 in breast cancer. Moon et al. (2015), using patient-derived xenograft (PDX) technique, sought to investigate the prognostic role and a gene signature in breast tumors of the triple-negative subtype. PHLDA2 was shown to be positively regulated in cells of the triple negative breast cancer subtype, and its silencing led to a reduction in invasion and proliferation of MDA-MB-231 cells, suggesting the involvement of PHLDA2 in the breast cancer.


Identification of differentially expressed genes associated with osteochondrosis in standardbred horses using RNA arbitrarily primed PCR
Austbø L, Røed KH, Dolvik NI, Skretting G
Anim Biotechnol 2010 Apr;21(2):135-9.
PMID 20379890
Tousled-like kinase 2 regulates recovery from a DNA damage-induced G2 arrest
Bruinsma W, van den Berg J, Aprelia M, Medema RH
EMBO Rep 2016 May;17(5):659-70.
PMID 26931568
The cBio cancer genomics portal: an open platform for exploring multidimensional cancer genomics data
Cerami E, Gao J, Dogrusoz U, Gross BE, Sumer SO, Aksoy BA, Jacobsen A, Byrne CJ, Heuer ML, Larsson E, Antipin Y, Reva B, Goldberg AP, Sander C, Schultz N
Cancer Discov 2012 May;2(5):401-4.
PMID 22588877
Gene profiling involved in immature CD4+ T lymphocyte responsible for systemic lupus erythematosus
Deng YJ, Huang ZX, Zhou CJ, Wang JW, You Y, Song ZQ, Xiang MM, Zhong BY, Hao F
Mol Immunol 2006 Mar;43(9):1497-507.
PMID 16143398
Dynamic interaction of DNA damage checkpoint protein Rad53 with chromatin assembly factor Asf1
Emili A, Schieltz DM, Yates JR, Hartwell LH
Mol Cell 2001 Jan;7(1):13-20.
PMID 11172707
Integrative analysis of complex cancer genomics and clinical profiles using the cBioPortal
Gao J, Aksoy BA, Dogrusoz U, Dresdner G, Gross B, Sumer SO, Sun Y, Jacobsen A, Sinha R, Larsson E, Cerami E, Sander C, Schultz N
Sci Signal 2013 Apr 2;6(269):pl1.
PMID 23550210
A Cross-Study Biomarker Signature of Human Bronchial Epithelial Cells Infected with Respiratory Syncytial Virus
Gardinassi LG
Adv Virol 2016;2016:3605302.
PMID 27274726
Human Tousled like kinases are targeted by an ATM- and Chk1-dependent DNA damage checkpoint
Groth A, Lukas J, Nigg EA, Silljé HH, Wernstedt C, Bartek J, Hansen K
EMBO J 2003 Apr 1;22(7):1676-87.
PMID 12660173
Spatial and temporal mapping of de novo mutations in schizophrenia to a fetal prefrontal cortical network
Gulsuner S, Walsh T, Watts AC, Lee MK, Thornton AM, Casadei S, Rippey C, Shahin H, , , Nimgaonkar VL, Go RC, Savage RM, Swerdlow NR, Gur RE, Braff DL, King MC, McClellan JM
Cell 2013 Aug 1;154(3):518-29.
PMID 23911319
PhosphoSitePlus, 2014: mutations, PTMs and recalibrations
Hornbeck PV, Zhang B, Murray B, Kornhauser JM, Latham V, Skrzypek E
Nucleic Acids Res 2015 Jan;43(Database issue):D512-20.
PMID 25514926
Asf1 links Rad53 to control of chromatin assembly
Hu F, Alcasabas AA, Elledge SJ
Genes Dev 2001 May 1;15(9):1061-6.
PMID 11331602
Genetic variation in the chromosome 17q23 amplicon and breast cancer risk
Kelemen LE, Wang X, Fredericksen ZS, Pankratz VS, Pharoah PD, Ahmed S, Dunning AM, Easton DF, Vierkant RA, Cerhan JR, Goode EL, Olson JE, Couch FJ
Cancer Epidemiol Biomarkers Prev 2009 Jun;18(6):1864-8.
PMID 19454617
Amplification of TLK2 Induces Genomic Instability via Impairing the G2-M Checkpoint
Kim JA, Anurag M, Veeraraghavan J, Schiff R, Li K, Wang XS
Mol Cancer Res 2016 Oct;14(10):920-927.
PMID 27489360
Comprehensive functional analysis of the tousled-like kinase 2 frequently amplified in aggressive luminal breast cancers
Kim JA, Tan Y, Wang X, Cao X, Veeraraghavan J, Liang Y, Edwards DP, Huang S, Pan X, Li K, Schiff R, Wang XS
Nat Commun 2016 Oct 3;7:12991.
PMID 27694828
Exploratory biomarker analysis for treatment response in KRAS wild type metastatic colorectal cancer patients who received cetuximab plus irinotecan
Kim ST, Ahn TJ, Lee E, Do IG, Lee SJ, Park SH, Park JO, Park YS, Lim HY, Kang WK, Kim SH, Lee J, Kim HC
BMC Cancer 2015 Oct 20;15:747.
PMID 26486455
Tousled-like kinases phosphorylate Asf1 to promote histone supply during DNA replication
Klimovskaia IM, Young C, Strømme CB, Menard P, Jasencakova Z, Mejlvang J, Ask K, Ploug M, Nielsen ML, Jensen ON, Groth A
Nat Commun 2014 Mar 6;5:3394.
PMID 24598821
Suppression of Tousled-like kinase activity after DNA damage or replication block requires ATM, NBS1 and Chk1
Krause DR, Jonnalagadda JC, Gatei MH, Sillje HH, Zhou BB, Nigg EA, Khanna K
Oncogene 2003 Sep 4;22(38):5927-37.
PMID 12955071
GSVD comparison of patient-matched normal and tumor aCGH profiles reveals global copy-number alterations predicting glioblastoma multiforme survival
Lee CH, Alpert BO, Sankaranarayanan P, Alter O
PLoS One 2012;7(1):e30098.
PMID 22291905
Tousled-like kinases stabilize replication forks and show synthetic lethality with checkpoint and PARP inhibitors
Lee SB, Segura-Bayona S, Villamor-Payà M, Saredi G, Todd MAM, Attolini CS, Chang TY, Stracker TH, Groth A
Sci Adv 2018 Aug 8;4(8):eaat4985.
PMID 30101194
Meta-analysis of 2,104 trios provides support for 10 new genes for intellectual disability
Lelieveld SH, Reijnders MR, Pfundt R, Yntema HG, Kamsteeg EJ, de Vries P, de Vries BB, Willemsen MH, Kleefstra T, Löhner K, Vreeburg M, Stevens SJ, van der Burgt I, Bongers EM, Stegmann AP, Rump P, Rinne T, Nelen MR, Veltman JA, Vissers LE, Brunner HG, Gilissen C
Nat Neurosci 2016 Sep;19(9):1194-6.
PMID 27479843
Inactive Tlk associating with Tak1 increases p38 MAPK activity to prolong the G2 phase
Liaw GJ, Chiang CS
Sci Rep 2019 Feb 13;9(1):1885.
PMID 30760733
TLK2 enhances aggressive phenotypes of glioblastoma cells through the activation of SRC signaling pathway
Lin M, Yao Z, Zhao N, Zhang C
Cancer Biol Ther 2019;20(1):101-108.
PMID 30207834
Proteogenomics connects somatic mutations to signalling in breast cancer
Mertins P, Mani DR, Ruggles KV, Gillette MA, Clauser KR, Wang P, Wang X, Qiao JW, Cao S, Petralia F, Kawaler E, Mundt F, Krug K, Tu Z, Lei JT, Gatza ML, Wilkerson M, Perou CM, Yellapantula V, Huang KL, Lin C, McLellan MD, Yan P, Davies SR, Townsend RR, Skates SJ, Wang J, Zhang B, Kinsinger CR, Mesri M, Rodriguez H, Ding L, Paulovich AG, Fenyö D, Ellis MJ, Carr SA,
Nature 2016 Jun 2;534(7605):55-62.
PMID 27251275
Molecular basis of Tousled-Like Kinase 2 activation
Mortuza GB, Hermida D, Pedersen AK, Segura-Bayona S, López-Méndez B, Redondo P, Rüther P, Pozdnyakova I, Garrote AM, Muñoz IG, Villamor-Payà M, Jauset C, Olsen JV, Stracker TH, Montoya G
Nat Commun 2018 Jun 28;9(1):2535.
PMID 29955062
Exome sequencing in sporadic autism spectrum disorders identifies severe de novo mutations
O', Roak BJ, Deriziotis P, Lee C, Vives L, Schwartz JJ, Girirajan S, Karakoc E, Mackenzie AP, Ng SB, Baker C, Rieder MJ, Nickerson DA, Bernier R, Fisher SE, Shendure J, Eichler EE
Nat Genet 2011 Jun;43(6):585-9.
PMID 21572417
Phosphorylation-mediated control of histone chaperone ASF1 levels by Tousled-like kinases
Pilyugin M, Demmers J, Verrijzer CP, Karch F, Moshkin YM
PLoS One 2009 Dec 16;4(12):e8328.
PMID 20016786
De Novo and Inherited Loss-of-Function Variants in TLK2: Clinical and Genotype-Phenotype Evaluation of a Distinct Neurodevelopmental Disorder
Reijnders MRF, Miller KA, Alvi M, Goos JAC, Lees MM, de Burca A, Henderson A, Kraus A, Mikat B, de Vries BBA, Isidor B, Kerr B, Marcelis C, Schluth-Bolard C, Deshpande C, Ruivenkamp CAL, Wieczorek D, , Baralle D, Blair EM, Engels H, Lüdecke HJ, Eason J, Santen GWE, Clayton-Smith J, Chandler K, Tatton-Brown K, Payne K, Helbig K, Radtke K, Nugent KM, Cremer K, Strom TM, Bird LM, Sinnema M, Bitner-Glindzicz M, van Dooren MF, Alders M, Koopmans M, Brick L, Kozenko M, Harline ML, Klaassens M, Steinraths M, Cooper NS, Edery P, Yap P, Terhal PA, van der Spek PJ, Lakeman P, Taylor RL, Littlejohn RO, Pfundt R, Mercimek-Andrews S, Stegmann APA, Kant SG, McLean S, Joss S, Swagemakers SMA, Douzgou S, Wall SA, Küry S, Calpena E, Koelling N, McGowan SJ, Twigg SRF, Mathijssen IMJ, Nellaker C, Brunner HG, Wilkie AOM
Am J Hum Genet 2018 Jun 7;102(6):1195-1203.
PMID 29861108
Whole genome paired-end sequencing elucidates functional and phenotypic consequences of balanced chromosomal rearrangement in patients with developmental disorders
Schluth-Bolard C, Diguet F, Chatron N, Rollat-Farnier PA, Bardel C, Afenjar A, Amblard F, Amiel J, Blesson S, Callier P, Capri Y, Collignon P, Cordier MP, Coubes C, Demeer B, Chaussenot A, Demurger F, Devillard F, Doco-Fenzy M, Dupont C, Dupont JM, Dupuis-Girod S, Faivre L, Gilbert-Dussardier B, Guerrot AM, Houlier M, Isidor B, Jaillard S, Joly-Hélas G, Kremer V, Lacombe D, Le Caignec C, Lebbar A, Lebrun M, Lesca G, Lespinasse J, Levy J, Malan V, Mathieu-Dramard M, Masson J, Masurel-Paulet A, Mignot C, Missirian C, Morice-Picard F, Moutton S, Nadeau G, Pebrel-Richard C, Odent S, Paquis-Flucklinger V, Pasquier L, Philip N, Plutino M, Pons L, Portnoï MF, Prieur F, Puechberty J, Putoux A, Rio M, Rooryck-Thambo C, Rossi M, Sarret C, Satre V, Siffroi JP, Till M, Touraine R, Toutain A, Toutain J, Valence S, Verloes A, Whalen S, Edery P, Tabet AC, Sanlaville D
J Med Genet 2019 Aug;56(8):526-535.
PMID 30923172
Differential requirements for Tousled-like kinases 1 and 2 in mammalian development
Segura-Bayona S, Knobel PA, González-Burón H, Youssef SA, Peña-Blanco A, Coyaud , López-Rovira T, Rein K, Palenzuela L, Colombelli J, Forrow S, Raught B, Groth A, de Bruin A, Stracker TH
Cell Death Differ 2017 Nov;24(11):1872-1885.
PMID 28708136
Identification of human Asf1 chromatin assembly factors as substrates of Tousled-like kinases
Silljé HH, Nigg EA
Curr Biol 2001 Jul 10;11(13):1068-73.
PMID 11470414
Evaluation of associations between common variation in mitotic regulatory pathways and risk of overall and high grade breast cancer
Stevens KN, Wang X, Fredericksen Z, Pankratz VS, Cerhan J, Vachon CM, Olson JE, Couch FJ
Breast Cancer Res Treat 2011 Sep;129(2):617-22.
PMID 21607584
Abeta42 generation is toxic to endothelial cells and inhibits eNOS function through an Akt/GSK-3beta signaling-dependent mechanism
Suhara T, Magrané J, Rosen K, Christensen R, Kim HS, Zheng B, McPhie DL, Walsh K, Querfurth H
Neurobiol Aging May-Jun 2003;24(3):437-51.
PMID 12600720
Severe neurodevelopmental disease caused by a homozygous TLK2 variant
Töpf A, Oktay Y, Balaraju S, Yilmaz E, Sonmezler E, Yis U, Laurie S, Thompson R, Roos A, MacArthur DG, Yaramis A, Güngör S, Lochmüller H, Hiz S, Horvath R
Eur J Hum Genet 2020 Mar;28(3):383-387.
PMID 31558842
Integrative Analyses of De Novo Mutations Provide Deeper Biological Insights into Autism Spectrum Disorder
Takata A, Miyake N, Tsurusaki Y, Fukai R, Miyatake S, Koshimizu E, Kushima I, Okada T, Morikawa M, Uno Y, Ishizuka K, Nakamura K, Tsujii M, Yoshikawa T, Toyota T, Okamoto N, Hiraki Y, Hashimoto R, Yasuda Y, Saitoh S, Ohashi K, Sakai Y, Ohga S, Hara T, Kato M, Nakamura K, Ito A, Seiwa C, Shirahata E, Osaka H, Matsumoto A, Takeshita S, Tohyama J, Saikusa T, Matsuishi T, Nakamura T, Tsuboi T, Kato T, Suzuki T, Saitsu H, Nakashima M, Mizuguchi T, Tanaka F, Mori N, Ozaki N, Matsumoto N
Cell Rep 2018 Jan 16;22(3):734-747.
PMID 29346770
Genetic regulatory network analysis for app based on genetical genomics approach
Wang X, Chen Y, Wang X, Lu L
Exp Aging Res Jan-Mar 2010;36(1):79-93.
PMID 20054728
cDNA cloning and chromosomal mapping of genes encoding novel protein kinases termed PKU-alpha and PKU-beta, which have nuclear localization signal
Yamakawa A, Kameoka Y, Hashimoto K, Yoshitake Y, Nishikawa K, Tanihara K, Date T
Gene 1997 Nov 20;202(1-2):193-201.
PMID 9427565
Nuclear localization of protein kinase U-alpha is regulated by 14-3-3
Zhang S, Xing H, Muslin AJ
J Biol Chem 1999 Aug 27;274(35):24865-72.
PMID 10455159


This paper should be referenced as such :
Gomes do Nascimento R, Mangone FR, Pavanelli C, Nagai MA
PHLDA2 (Pleckstrin homology-like domain, family A, member 2);
Atlas Genet Cytogenet Oncol Haematol. in press

External links

HGNC (Hugo)PHLDA2   12385
LRG (Locus Reference Genomic)LRG_1043
Entrez_Gene (NCBI)PHLDA2    pleckstrin homology like domain family A member 2
AliasesBRW1C; BWR1C; HLDA2; IPL; 
GeneCards (Weizmann)PHLDA2
Ensembl hg19 (Hinxton)ENSG00000181649 [Gene_View]
Ensembl hg38 (Hinxton)ENSG00000181649 [Gene_View]  ENSG00000181649 [Sequence]  chr11:2928273-2929420 [Contig_View]  PHLDA2 [Vega]
ICGC DataPortalENSG00000181649
Genatlas (Paris)PHLDA2
SOURCE (Princeton)PHLDA2
Genetics Home Reference (NIH)PHLDA2
Genomic and cartography
GoldenPath hg38 (UCSC)PHLDA2  -     chr11:2928273-2929420 -  11p15.4   [Description]    (hg38-Dec_2013)
GoldenPath hg19 (UCSC)PHLDA2  -     11p15.4   [Description]    (hg19-Feb_2009)
GoldenPathPHLDA2 - 11p15.4 [CytoView hg19]  PHLDA2 - 11p15.4 [CytoView hg38]
genome Data Viewer NCBIPHLDA2 [Mapview hg19]  
Gene and transcription
Genbank (Entrez)AF001294 AF019953 AF035444 AI659266 AK223027
RefSeq transcript (Entrez)NM_003311
RefSeq genomic (Entrez)NC_000011 NG_009266 NT_187585
Consensus coding sequences : CCDS (NCBI)PHLDA2
Alternative Splicing GalleryENSG00000181649
Gene ExpressionPHLDA2 [ NCBI-GEO ]   PHLDA2 [ EBI - ARRAY_EXPRESS ]   PHLDA2 [ SEEK ]   PHLDA2 [ MEM ]
Gene Expression Viewer (FireBrowse)PHLDA2 [ Firebrowse - Broad ]
GenevisibleExpression of PHLDA2 in : [tissues]  [cell-lines]  [cancer]  [perturbations]  
BioGPS (Tissue expression)7262
GTEX Portal (Tissue expression)PHLDA2
Human Protein AtlasENSG00000181649-PHLDA2 [pathology]   [cell]   [tissue]
Protein : pattern, domain, 3D structure
UniProt/SwissProtQ53GA4   [function]  [subcellular_location]  [family_and_domains]  [pathology_and_biotech]  [ptm_processing]  [expression]  [interaction]
NextProtQ53GA4  [Sequence]  [Exons]  [Medical]  [Publications]
With graphics : InterProQ53GA4
Splice isoforms : SwissVarQ53GA4
Domains : Interpro (EBI)PH-like_dom_sf    PH_domain    PHLA1/2/3    PHLA2/3_PH   
Domain families : Pfam (Sanger)PH_15 (PF17339)   
Domain families : Pfam (NCBI)pfam17339   
Domain families : Smart (EMBL)PH (SM00233)  
Conserved Domain (NCBI)PHLDA2
Blocks (Seattle)PHLDA2
Human Protein Atlas [tissue]ENSG00000181649-PHLDA2 [tissue]
Peptide AtlasQ53GA4
Protein Interaction databases
IntAct (EBI)Q53GA4
Ontologies - Pathways
Ontology : AmiGOplacenta development  cytoplasm  apoptotic process  animal organ morphogenesis  regulation of gene expression  membrane  regulation of cell migration  positive regulation of apoptotic process  regulation of spongiotrophoblast cell proliferation  regulation of glycogen metabolic process  phosphatidylinositol phosphate binding  regulation of growth hormone activity  
Ontology : EGO-EBIplacenta development  cytoplasm  apoptotic process  animal organ morphogenesis  regulation of gene expression  membrane  regulation of cell migration  positive regulation of apoptotic process  regulation of spongiotrophoblast cell proliferation  regulation of glycogen metabolic process  phosphatidylinositol phosphate binding  regulation of growth hormone activity  
NDEx NetworkPHLDA2
Atlas of Cancer Signalling NetworkPHLDA2
Wikipedia pathwaysPHLDA2
Orthology - Evolution
GeneTree (enSembl)ENSG00000181649
Phylogenetic Trees/Animal Genes : TreeFamPHLDA2
Homologs : HomoloGenePHLDA2
Homology/Alignments : Family Browser (UCSC)PHLDA2
Gene fusions - Rearrangements
Fusion : Fusion_HubFSCN1--PHLDA2    HNRNPK--PHLDA2   
Fusion : QuiverPHLDA2
Polymorphisms : SNP and Copy number variants
NCBI Variation ViewerPHLDA2 [hg38]
Exome Variant ServerPHLDA2
GNOMAD BrowserENSG00000181649
Varsome BrowserPHLDA2
Genomic Variants (DGV)PHLDA2 [DGVbeta]
DECIPHERPHLDA2 [patients]   [syndromes]   [variants]   [genes]  
CONAN: Copy Number AnalysisPHLDA2 
ICGC Data PortalPHLDA2 
TCGA Data PortalPHLDA2 
Broad Tumor PortalPHLDA2
OASIS PortalPHLDA2 [ Somatic mutations - Copy number]
Somatic Mutations in Cancer : COSMICPHLDA2  [overview]  [genome browser]  [tissue]  [distribution]  
Somatic Mutations in Cancer : COSMIC3DPHLDA2
Mutations and Diseases : HGMDPHLDA2
LOVD (Leiden Open Variation Database)Whole genome datasets
LOVD (Leiden Open Variation Database)LOVD 3.0 shared installation
BioMutasearch PHLDA2
DgiDB (Drug Gene Interaction Database)PHLDA2
DoCM (Curated mutations)PHLDA2 (select the gene name)
CIViC (Clinical Interpretations of Variants in Cancer)PHLDA2 (select a term)
NCG6 (London) select PHLDA2
Cancer3DPHLDA2(select the gene name)
Impact of mutations[PolyPhen2] [Provean] [Buck Institute : MutDB] [Mutation Assessor] [Mutanalyser]
Genetic Testing Registry PHLDA2
NextProtQ53GA4 [Medical]
Target ValidationPHLDA2
Huge Navigator PHLDA2 [HugePedia]
ClinGenPHLDA2 (curated)
Clinical trials, drugs, therapy
Protein Interactions : CTD
Pharm GKB GenePA37053
Clinical trialPHLDA2
canSAR (ICR)PHLDA2 (select the gene name)
DataMed IndexPHLDA2
PubMed43 Pubmed reference(s) in Entrez
GeneRIFsGene References Into Functions (Entrez)
REVIEW articlesautomatic search in PubMed
Last year publicationsautomatic search in PubMed

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indexed on : Fri Feb 19 17:57:27 CET 2021

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